Sequential CD19- and CD22-CART Cell Therapies for Relapsed B-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

With traditional therapies, the prognosis of relapsed acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor. Chimeric antigen receptor (CAR) T cell therapy targeting at CD19 has demonstrated a significant efficacy on refractory/relapsed (r/r) B-ALL, but single-target CART could not maintain a long-term remission. Recently, CD22-CART has also shown an exciting result in r/r B-ALL. Here we sequentially applied CD19- and CD22-specific CART cells to treat relapsed B-ALL post-HSCT and observed the therapeutic effect.From June 30,2017 through May 31,2018, twenty-four B-ALL patients (pts) relapsing after allo-HSCT with both antigens CD19 and CD22 expression on blasts were enrolled, the median age was 24 (2.3-55) years. Seventeen pts had hematologic relapse, 6 with both bone marrow and extramedullary (EM) involvements and 1 with EM disease (EMD) only. Fourteen pts had failed to previous therapies including chemotherapy, donor lymphocyte infusion, interferon and even murinized CD19-CART in other hospitals.Recipient-derived donor T cells were collected for producing CAR-T cells, which were transfected by a lentiviral vector encoding the CAR composed of CD3 and 4-1BB. Eighteen pts were initially infused with murinized CD19-CART, then humanized CD22-CART; while 6 pts (5 failed to prior murinized CD19-CART and 1 had bright CD22-expression) were initially infused with humanized CD22-CART, then humanized CD19-CART. The time...
Source: Blood - Category: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster I Source Type: research

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Donor cell (DC) leukemia is a rare cause of relapse after allogeneic hematopoietic cell transplantation and usually presents as acute myeloid leukemia. Uncommonly, other DC ‐derived hematologic malignancies can occur and usually have a poor prognosis. AbstractDonor cell leukemia is a very rare cause of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Herein, we describe an unprecedented case of donor cell ‐derived chronic myelomonocytic leukemia (CMML) presenting seven years after a 51‐year‐old man received a matched‐related alloHCT from his 59‐year‐old brother for T‐cell acute lymphoblastic leukemia.
Source: Clinical Case Reports - Category: General Medicine Authors: Tags: CASE REPORT Source Type: research
o Nicolotti The fusion oncoprotein Bcr-Abl is an aberrant tyrosine kinase responsible for chronic myeloid leukemia and acute lymphoblastic leukemia. The auto-inhibition regulatory module observed in the progenitor kinase c-Abl is lost in the aberrant Bcr-Abl, because of the lack of the N-myristoylated cap able to bind the myristoyl binding pocket also conserved in the Bcr-Abl kinase domain. A way to overcome the occurrence of resistance phenomena frequently observed for Bcr-Abl orthosteric drugs is the rational design of allosteric ligands approaching the so-called myristoyl binding pocket. The discovery of these allos...
Source: Molecules - Category: Chemistry Authors: Tags: Perspective Source Type: research
In this study, the CML model was used to test if TKIs would sustain or not the viral replication and if they could damage patient immunity. Firstly, the infection and replication rate of torquetenovirus (TTV), whose load is inversely proportional to the host immunological control, have been measured in CML patients receiving nilotinib. A very low percentage of subjects were infected at baseline, and TTV did not replicate or at least showed a low replication rate during the follow-up, with a mean load comparable to the measured one in healthy subjects. Then, after gene expression profiling experiments, we found that several...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: We developed a highly sensitive and selective HPLC-MS/MS method to quantify PNT in human plasma. This method might be used for TDM and to guide dose reductions if unnecessary high PNT levels are detected in a patient.Chemotherapy
Source: Chemotherapy - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses. PMID: 32818321 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
In this study, we present a case of ALL who was diagnosed with CCHF simultaneously. A 43-year old female patient who works in the library and does not have a chronic disease other than asthma and thyroid disorder, has admitted to our hospital with the complaints of intermittent fever, weakness, generalized joint and body pain for about 3 weeks. She had fever and the physical examination revealed bilateral cervical and right postauricular lymphadenopathies. Her aspartate aminotransferase: 77 U/L, alanine aminotransferase: 117 U/L, lactate dehydrogenase: 616 U/L, hemoglobin: 8.27 g/dl, leukocyte count: 15.690/mm3 , neutrophi...
Source: Mikrobiyoloji Bulteni - Category: Microbiology Tags: Mikrobiyol Bul Source Type: research
The clonoSEQ ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) identifies and tracks unique disease-associated immunoglobulin (Ig) sequences by next-generation sequencing of IgH, IgK, and IgL rearran...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
AbstractTo explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectiv...
Source: Annals of Hematology - Category: Hematology Source Type: research
ConclusionsA significant decrease in leukemia incidence was observed between 1990 and 2017. However, in the same period, the incidence rates of AML and CLL significantly increased in most countries, suggesting that both types of leukemia might become a major global public health concern.
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
Authors: Chen X, Yu X, Wang DD, Xu H, Li Z Abstract Bone marrow transplants (BMT) are an established therapeutic strategy for patients with severe aplastic anemia, acute lymphoblastic leukemia, acute myeloid leukemia or chronic myeloid leukemia. However, the successful application of BMT is limited by graft-vs.-host disease (GVHD). Ciclosporin has been widely used for treating GVHD in pediatric patients who underwent BMT. The present study aimed to optimize the dosage of ciclosporin for safety and effectiveness based on population pharmacokinetics. A non-linear mixed-effects model was used to analyze the clinical d...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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